Taysha Gene Therapies (TSHA) Study result summary

Program and Study Overview

• Dosing completed in the REVEAL pivotal trial for TSHA-102 in Rett syndrome, enrolling 17 patients aged 6–21 years, with a single-arm, open-label design and intrathecal administration.

• The primary endpoint is the response rate, defined as the percentage of patients gaining or regaining one or more of 28 developmental milestones, with each patient serving as their own control.

• A six-month interim analysis is planned, which may serve as the basis for a BLA submission, potentially expediting regulatory review.

• The ASPIRE safety-focused trial for younger patients (aged 2–4) is ongoing, with dosing exceeding initial targets and expected to complete by July 2026.

• TSHA-102 is a one-time, intrathecally delivered AAV9 gene therapy designed to address the genetic root cause of Rett syndrome by delivering functional MECP2 to CNS cells.

Efficacy and Functional Gains

• All 12 treated patients in REVEAL Part A achieved at least one developmental milestone at 12 months, yielding a 100% response rate, with consistent responses across ages and disease severity.

• Functional gains increased by 69% from month 6 to 12 and by 94% from 6 to ≥12 months post-treatment.

• At ≥12 months, patients averaged 26 functional gains, including improvements in communication, fine and gross motor skills, daily living activities, and additional skills.

• Statistically significant improvements were seen in R-MBA and CGI-I scores, with all patients showing improved CGI-I scores and high-dose patients achieving faster, greater improvements.

• Durable, multi-domain gains enabled greater independence, reduced caregiver burden, and enhanced social engagement.

Functional and Quality of Life Impact

• Patients gained key communication, fine motor, and gross motor skills, such as speaking in phrases, self-feeding, and walking with support.

• Caregiver testimonials and patient vignettes highlighted substantial improvements in independence, social engagement, and reduction in caregiver burden.

• Notable reductions in seizure frequency and improvements in breathing dysrhythmia were observed.

• Functional gains were achieved without additional supportive therapies beyond standard care.

• Functional gains included both developmental milestones and additional skills, such as reduced stereotypies and improved social engagement.